Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: support for an endothelium-dependent mechanism.
In: Cardiovascular research, Jg. 69 (2006-03-01), Heft 4, S. 925-35
Online
academicJournal
Zugriff:
Objective: Studies have reported that administration of stromal cell-derived factor-1 (SDF-1), the ligand for the G-protein coupled receptor CXCR4, increased collateral blood flow in a mouse model of vascular insufficiency via recruitment of endothelial precursor cells (EPC). The present study investigated the contribution of mature endothelial cells in the actions of SDF-1.
Methods: The regulation of SDF-1 and CXCR4 was examined in the rat cornea cauterization (CC) and aortic ring (AR) model. The functional significance of the SDF-1/CXCR4 pathway was explored in cultured endothelial cells, the AR model, and on collateral blood flow in a rat model of vascular insufficiency.
Results: In the present study, the CXCR4 transcript was dramatically upregulated in the rat CC and AR explants, systems containing and lacking bone marrow-derived EPCs, respectively. Addition of AMD3100, a selective CXCR4 antagonist, had no effect on vessel growth in the AR alone, but completely inhibited SDF-1 mediated increases in vascular sprouting. In cultured endothelial cells, SDF-1 alone or in combination with vascular endothelial growth factor (VEGF) significantly enhanced cell survival and migration. Finally, systemic administration of SDF-1 in a rat model of arterial insufficiency enhanced collateral blood flow above vehicle control and equal to that of VEGF after 2 weeks of treatment.
Conclusion: These studies support activation of the SDF-1/CXCR4 axis as a means to promote blood vessel growth and enhance collateral blood flow, at least in part, via direct effects on vascular endothelial cells.
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Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: support for an endothelium-dependent mechanism.
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Autor/in / Beteiligte Person: | Carr, AN ; Howard, BW ; Yang, HT ; Eby-Wilkens, E ; Loos, P ; Varbanov, A ; Qu, A ; DeMuth, JP ; Davis, MG ; Proia, A ; Terjung, RL ; Peters, KG |
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Zeitschrift: | Cardiovascular research, Jg. 69 (2006-03-01), Heft 4, S. 925-35 |
Veröffentlichung: | 2008- : Oxford : Oxford Journals ; <i>Original Publication</i>: London, British Medical Assn., 2006 |
Medientyp: | academicJournal |
ISSN: | 0008-6363 (print) |
DOI: | 10.1016/j.cardiores.2005.12.005 |
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